Agnes M.M. Sonnenschein-van der Voort

Early growth characteristics and the risk of reduced lung function and asthma : A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Tobacco Smoke Exposure, Airway Resistance, and Asthma in School-age Children: The Generation R Study

BACKGROUND Tobacco smoke exposure has been associated with early childhood asthma symptoms. We assessed the associations of tobacco smoke exposure during pregnancy and childhood with wheezing patterns, asthma, airway interrupter resistance (Rint), and fractional exhaled nitric oxide (Feno) in school-age children and whether birth characteristics explained the associations. METHODS This study was embedded in a population-based prospective cohort study among 6,007 children. Paternal and maternal smoking during pregnancy (never, first trimester only, continued), secondhand tobacco smoke exposure during childhood, wheezing patterns, and asthma were prospectively assessed by questionnaires. Wheezing patterns were defined as never, early (≤ 3 years only), late (> 3 years only), and persistent (≤ 3 and > 3 years) wheezing. Rint and Feno were measured at age 6 years. Birth characteristics were available from registries. RESULTS Continued maternal smoking during pregnancy was associated with increased risks of early and persistent wheezing (OR: 1.24 [1.01, 1.52]; 1.48 [1.13, 1.95]) and asthma (1.65 [1.07, 2.55], for at least five cigarettes per day), but not with Rint or Feno. Birth characteristics did not explain these associations. Childhood tobacco smoke exposure was associated with higher Rint (difference z score: 0.45 [0.00, 0.90]), but this effect attenuated after adjustment for birth characteristics. Maternal smoking during first trimester only or paternal smoking during pregnancy was not associated with Rint, Feno, wheezing, or asthma. CONCLUSIONS Continued maternal smoking during pregnancy was associated with increased risks of asthma outcomes in school-age children, whereas childhood tobacco smoke exposure was associated with higher Rint. Birth characteristics may explain part of these associations.

Air pollution, fetal and infant tobacco smoke exposure, and wheezing in preschool children: a population-based prospective birth cohort

BackgroundAir pollution is associated with asthma exacerbations. We examined the associations of exposure to ambient particulate matter (PM10) and nitrogen dioxide (NO2) with the risk of wheezing in preschool children, and assessed whether these associations were modified by tobacco smoke exposure.MethodsThis study was embedded in the Generation R Study, a population-based prospective cohort study among 4,634 children. PM10 and NO2 levels were estimated for the home addresses using dispersion modeling. Annual parental reports of wheezing until the age of 3 years and fetal and infant tobacco smoke exposure was obtained by questionnaires.ResultsAverage annual PM10 or NO2 exposure levels per year were not associated with wheezing in the same year. Longitudinal analyses revealed non-significant tendencies towards positive associations of PM10 or NO2 exposure levels with wheezing during the first 3 years of life (overall odds ratios (95% confidence interval): 1.21 (0.79, 1.87) and 1.06 (0.92, 1.22)) per 10 μg/m3 increase PM10 and NO2, respectively). Stratified analyses showed that the associations were stronger and only significant among children who were exposed to both fetal and infant tobacco smoke (overall odds ratios 4.54 (1.17, 17.65) and 1.85 (1.15, 2.96)) per 10 μg/m3 increase PM10 and NO2, respectively (p-value for interactions <0.05).ConclusionsOur results suggest that long term exposure to traffic-related air pollutants is associated with increased risks of wheezing in children exposed to tobacco smoke in fetal life and infancy. Smoke exposure in early life might lead to increased vulnerability of the lungs to air pollution.

Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts

BACKGROUND Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient. METHODS A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring. Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥ 30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12-24 months of age. Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model. RESULTS The study included 85509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98-1.06) and 1.20 (95% CI: 0.98-1.47) for hypertensive disorders; 1.09 (95% CI: 1.01-1.18) and 1.23 (95% CI: 1.07-1.43) for preeclampsia; 1.04 (95% CI: 0.97-1.13) and 1.24 (95% CI: 0.86-1.79) for diabetes; 1.08 (95% CI: 1.05-1.11) and 1.19 (95% CI: 1.12-1.26) for overweight; 1.12 (95% CI: 1.08-1.17) and 1.16 (95% CI: 0.97-1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P=0.027). CONCLUSIONS Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.

Breastfeeding and asthma outcomes at the age of 6 years: The Generation R Study.

Breastfeeding is associated with a lower risk of asthma symptoms in early childhood, but its effect at older ages remains unclear. We examined the associations of duration and exclusiveness of breastfeeding with asthma outcomes in children aged 6 years, and whether these associations were explained by atopic or infectious mechanisms.

Foetal and infant growth patterns, airway resistance and school-age asthma.

Preterm birth, low birth weight and rapid infant weight gain are associated with increased risks of asthma symptoms in childhood. The underlying mechanism may include persistently higher airway resistance (Rint). The aim of our study was to examine the associations of longitudinally measured foetal and infant growth characteristics with Rint and asthma outcomes in school‐age children.

Influence of maternal and cord blood C-reactive protein on childhood respiratory symptoms and eczema.

Inflammatory processes during pregnancy might affect fetal lung development and immune responses. We examined the associations of maternal and cord blood C‐reactive protein levels with respiratory symptoms and eczema in preschool children.

Is parent–child bed-sharing a risk for wheezing and asthma in early childhood?

Household crowding can place young children at risk for respiratory infections which subsequently provoke asthma symptoms. However, crowding might also protect against asthma, in accordance with the hygiene hypothesis. We tested if parent–infant bed-sharing, an important dimension of household crowding, increases or decreases the risk for asthma. In a population-based prospective cohort (N = 6160) we assessed bed-sharing at 2 and 24 months; wheezing between 1 and 6 years of age; and asthma at 6 years of age. Generalised estimating equation models were used to assess repeated measures of wheezing and asthma. We found no association between bed-sharing in early infancy and wheezing or diagnosis of asthma. By contrast, we found a positive association between bed-sharing in toddlerhood and both wheezing (OR 1.42, 95% CI 1.15–1.74) and asthma (OR 1.57, 95% CI 1.03–2.38). Wheezing was not associated with bed-sharing when using cross-lagged modelling. This study suggests that bed-sharing in toddlerhood is associated with an increased risk of asthma at later ages, and not vice versa. Further studies are needed to explore the underlying causal mechanisms. More wheezing and asthma reported for bed-sharing toddlers, not for infants: parental vigilance or increased risk? http://ow.ly/Dgy4v

Socioeconomic and sociodemographic factors associated with asthma related outcomes in early childhood: The generation R study

Rationale Few studies have analyzed the association of socioeconomic and sociodemographic factors with asthma related outcomes in early childhood, including Fraction of exhaled Nitric Oxide (FeNO) and airway resistance (Rint). We examined the association of socioeconomic and sociodemographic factors with wheezing, asthma, FeNO and Rint at age 6 years. Additionally, the role of potential mediating factors was studied. Methods The study included 6717 children participating in The Generation R Study, a prospective population-based cohort study. Data on socioeconomic and sociodemographic factors, wheezing and asthma were obtained by questionnaires. FeNO and Rint were measured at the research center. Statistical analyses were performed using logistic and linear regression models. Results At age 6 years, 9% (456/5084) of the children had wheezing symptoms and 7% (328/4953) had asthma. Children from parents with financial difficulties had an increased risk of wheezing (adjusted Odds Ratio (aOR) = 1.63, 95% Confidence Interval (CI):1.18–2.24). Parental low education, paternal unemployment and childs male sex were associated with asthma, independent of other socioeconomic or sociodemographic factors (aOR = 1.63, 95% CI:1.24–2.15, aOR = 1.85, 95% CI:1.11–3.09, aOR = 1.58, 95% CI:1.24–2.01, respectively). No socioeconomic or gender differences in FeNO were found. The risks of wheezing, asthma, FeNO and Rint measurements differed between ethnic groups (p<0.05). Associations between paternal unemployment, childs sex, ethnicity and asthma related outcomes remained largely unexplained. Conclusions This study showed differences between the socioeconomic and sociodemographic correlates of wheezing and asthma compared to the correlates of FeNO and Rint at age 6 years. Several socioeconomic and sociodemographic factors were independently associated with wheezing and asthma. Childs ethnicity was the only factor independently associated with FeNO. We encourage further studies on underlying pathways and public health intervention programs, focusing on reducing socioeconomic or sociodemographic inequalities in asthma.

Role of environmental exposures and filaggrin mutations on associations of ethnic origin with risk of childhood eczema. The Generation R Study

The prevalence of childhood eczema varies considerably between ethnic groups. However, data from longitudinal studies remain scarce.